The brain has the capability of becoming less vulnerable to stroke. In this proposal, the endogenous development of neuronal protection, through sublethal exposure to oxygen-glucose deprivation, will be studied using an in vitro model which has been established by the applicant. The model, coined "Cerebral preconditioning in Cortical Cell Culture" (CPC) will first be explored in further detail as to the extent of protection this sublethal stress has on other neuronal injury paradigms. In the next set of experiments, further characterization of the phenomenon will be initiated to explore methods of mimicking the phenomenon pharmacologically. Finally, pre and postsynaptic alterations will be studied to determine the dependence of both for the development of CPC. Presynaptically the cause of the lowered glutamate release will be defined, while postsynaptically, glutamate receptor alterations and synthesis of specific proteins will be measured. From these results, scientists will have a better handle of the probable mechanisms involved, and studies can then turn to initiating these mechanisms for clinical use.